Microbial Diseases of the Respiratory System Chapter 24 Microbial Diseases of the Respiratory System Lectures prepared by Christine L. Case © 2013 Pearson Education, Inc. 1

Figure 24.1 Structures of the upper respiratory system. Sinus Middle ear Sinus Nasal cavity Auditory (eustachian) tube Opening of auditory tube Oral cavity Tongue Tonsils Epiglottis Pharynx (throat) Layrnx (voice box) Spine (backbone) Esophagus Trachea (windpipe)

Figure 24.2 Structures of the lower respiratory system. Branch from the pulmonary artery Bronchiole Blood capillaries Branch from the pulmonary vein Pharynx (throat) Larynx (voice box) Left lung Trachea (windpipe) Right lung Alveoli Bronchus Bronchiole Pleura Heart Diaphragm (breathing muscle)

Normal Microbiota of the Respiratory System Suppress pathogens by competitive inhibition in upper respiratory system Lower respiratory system is sterile

Upper Respiratory System Diseases Pharyngitis Laryngitis Tonsillitis Sinusitis Epiglottitis: H. influenzae type b

Streptococcal Pharyngitis Also called strep throat Streptococcus pyogenes Resistant to phagocytosis Streptokinases lyse clots Streptolysins are cytotoxic Diagnosis by enzyme immunoassay (EIA) tests Scarlet fever Erythrogenic toxin produced by lysogenized S. pyogenes

Figure 24.3 Streptococcal pharyngitis.

Clubbed cells Palisade arrangement Figure 24.4 Corynebacterium diphtheriae, the cause of diphtheria. Clubbed cells Palisade arrangement

Figure 24.5 A diphtheria membrane. Membrane on tonsils

Diphtheria Corynebacterium diphtheriae: gram-positive rod Diphtheria toxin produced by lysogenized C. diphtheriae Prevented by DTaP vaccine Diphtheria toxoid Cutaneous diphtheria Infected skin wound leads to slow-healing ulcer

Otitis Media S. pneumoniae (35%) H. influenzae (20–30%) M. catarrhalis (10–15%) S. pyogenes (8–10%) S. aureus (1–2%) Incidence of S. pneumoniae reduced by vaccine

Figure 24.6 Acute otitis media, with bulging eardrum.

The Common Cold Rhinoviruses (30–50%) Coronaviruses (10–15%)

Diseases in Focus: Diseases of the Upper Respiratory System A patient presents with fever and a red, sore throat. Later, a grayish membrane appears in the throat. Gram-positive rods are cultured from the membrane. Can you identify infections that could cause these symptoms?

Characteristic swollen lymph nodes of this disease. Diseases in Focus: Microbial Diseases of the Upper Respiratory System Characteristic swollen lymph nodes of this disease.

Lower Respiratory System Diseases Bacteria, viruses, and fungi cause Bronchitis Bronchiolitis Pneumonia

Pertussis (Whooping Cough) Bordetella pertussis Gram-negative coccobacillus Capsule Tracheal cytotoxin of cell wall damages ciliated cells Pertussis toxin Prevented by DTaP vaccine (acellular Pertussis cell fragments)

Figure 24.7 Ciliated cells of the respiratory system infected with Bordetella pertussis. B. pertussis Cilia © 2013 Pearson Education, Inc.

Pertussis (Whooping Cough) Stage 1: catarrhal stage, like common cold Stage 2: paroxysmal stage—violent coughing sieges Stage 3: convalescence stage

Figure 24.8 Mycobacterium tuberculosis. Corded growth

Tuberculosis Mycobacterium tuberculosis Acid-fast rod; transmitted human-to-human M. bovis: <1% of U.S. cases; not transmitted from human to human M. avium-intracellulare complex infects people with late-stage HIV infection

Reported tuberculosis cases, 1948–2010 Figure 14.10c Epidemiological graphs. 120 100 80 60 40 20 Reported cases per 100,000 people 1948 1958 1968 1978 1988 1998 2008 Year Reported tuberculosis cases, 1948–2010

Estimated tuberculosis incidence worldwide, per 100,000 population Figure 24.11a Distribution of tuberculosis. 0 – 24 100 – 299 25 – 49 _ > 300 50 – 99 Estimated tuberculosis incidence worldwide, per 100,000 population

Reported cases per 100,000 population Figure 24.11b Distribution of tuberculosis. Reported tuberculosis cases per 100,000 population among American ethnic groups in 2009 Asian and Pacific Islanders Black, non-Hispanic Hispanic American Indian/ Alaskan native White, non-Hispanic 0 5 10 15 20 25 30 Reported cases per 100,000 population

Interior of alveolus Blood capillary Alveolar walls Figure 24.9.1 The pathogenesis of tuberculosis. Interior of alveolus Blood capillary Alveolar walls Interior of alveolus Ingested tubercle bacillus Alveolar macrophage Bronchiole Tubercle bacilli that reach the alveoli of the lung (see Figure 24.2) are ingested by macrophages, but often some survive. Infection is present, but no symptoms of disease. 1

Infiltrating macrophage (not activated) Figure 24.9.2 The pathogenesis of tuberculosis. Infiltrating macrophage (not activated) Early tubercle Tubercle bacilli multiplying in macrophages cause a chemotactic response that brings additional macrophages and other defensive cells to the area. These form a surrounding layer and, in turn, an early tubercle. Most of the surrounding macrophages are not successful in destroying bacteria but release enzymes and cytokines that cause a lung-damaging inflammation. 2

Activated macrophages Figure 24.9.3 The pathogenesis of tuberculosis. Tubercle bacillus Caseous center Activated macrophages Lymphocyte After a few weeks, disease symptoms appear as many of the macrophages die, releasing tubercle bacilli and forming a caseous center in the tubercle. The aerobic tubercle bacilli do not grow well in this location. However, many remain dormant (latent TB) and serve as a basis for later reactivation of the disease. The disease may be arrested at this stage, and the lesions become calcified. 3

Outer layer of mature tubercle Figure 24.9.4 The pathogenesis of tuberculosis. Outer layer of mature tubercle Tuberculous cavity Tubercle bacillus 4 In some individuals, disease symptoms appear as a mature tubercle is formed. The disease progresses as the caseous center enlarges in the process called liquefaction. The caseous center now enlarges and forms an air-filled tuberculous cavity in which the aerobic bacilli multiply outside the macrophages.

Rupture of alveolar wall Figure 24.9.5 The pathogenesis of tuberculosis. Rupture of alveolar wall 5 Liquefaction continues until the tubercle ruptures, allowing bacilli to spill into a bronchiole (see Figure 24.2) and thus be disseminated throughout the lungs and then to the circulatory and lymphatic systems.

Treatment of Tuberculosis Treatment: prolonged treatment with multiple antibiotics Vaccines: BCG vaccine, live culture of avirulent M. bovis; not widely used in United States

Figure 24.10 A positive tuberculin skin test on an arm.

Diagnosis of Tuberculosis Tuberculin skin test screening Positive reaction means current or previous infection Followed by X-ray or CT exam, acid-fast staining of sputum, culturing of bacteria

Figure 24.12 Streptococcus pneumoniae, the cause of pneumococcal pneumonia. Paired cocci Capsule © 2013 Pearson Education, Inc.

Pneumococcal Pneumonia Streptococcus pneumoniae: encapsulated diplococci Symptoms: infected alveoli of lung fill with fluids; interferes with oxygen uptake Diagnosis: optochin-inhibition test or bile solubility test; serological typing of bacteria Treatment: macrolides, fluoroquinolones Prevention: pneumococcal vaccine

Haemophilus influenzae Pneumonia Gram-negative coccobacillus Predisposing factors: alcoholism, poor nutrition, cancer, or diabetes Symptoms: resemble those of pneumococcal pneumonia Diagnosis: isolation; special media for nutritional requirements Treatment: cephalosporins

Mycoplasmal Pneumonia Primary atypical pneumonia; walking pneumonia Mycoplasma pneumoniae Pleomorphic, wall-less bacteria Common in children and young adults

Figure 24.13 Colonies of Mycoplasma pneumoniae, the cause of mycoplasmal pneumonia.

Figure 11.18b Mycloplasma pneumoniae. This micrograph shows the filamentous growth of M. pneumoniae. Some individual cells can also be seen (arrow). The organism reproduces by fragmentation of the filament at the bulges.

Mycoplasmal Pneumonia Symptoms: mild but persistent respiratory symptoms; low fever, cough, headache Diagnosis: PCR and serological testing Treatment: tetracyclines

Legionellosis Legionella pneumophila Found in water Gram-negative rod Found in water Transmitted by inhaling aerosols; not transmitted from human to human

Legionellosis Symptoms: potentially fatal pneumonia that tends to affect older men who drink or smoke heavily Diagnosis: culture on selective media, DNA probe Treatment: erythromycin

Psittacosis (Ornithosis) Chlamydophila psittaci Gram-negative intracellular bacterium Transmitted to humans by elementary bodies from bird droppings Reorganizes into reticulate body after being phagocytized

Psittacosis (Ornithosis) Symptoms: symptoms, if any, are fever, headache, chills Diagnosis: growth of bacteria in eggs or cell culture Treatment: tetracyclines

Elementary body Reticulate body Intermediate body Figure 11.22b Chlamydias Elementary body Reticulate body Intermediate body Micrograph of Chlamydophila psittaci in the cytoplasm of a host cell. The elementary bodies are the infectious stage; they are dense, dark, and relatively small. Reticulate bodies, the form in which chlamydias reproduce within the host cell, are larger with a speckled appearance. Intermediate bodies, a stage between the two, have a dark center.

Chlamydial Pneumonia Chlamydophila pneumoniae Transmitted from human to human Symptoms: mild respiratory illness common in young people; resembles mycoplasmal pneumonia Diagnosis: serological tests Treatment: tetracyclines

Q Fever Causative agent: Coxiella burnetii Reservoir: large mammals Tick vector Can be transmitted via unpasteurized milk

E Figure 24.14 Coxiella burnetii, the cause of Q fever. Masses of Coxiella burnetii growing in a placental cell. This cell has just divided; notice the endospore-like body (E), which is probably responsible for the relative resistance of the organism.

Q Fever Symptoms: mild respiratory disease lasting 1–2 weeks; occasional complications such as endocarditis occur Diagnosis: growth in cell culture Treatment: doxycycline and chloroquine

Melioidosis Causative agent: Burkholderia pseudomallei Reservoir: soil Mainly in southeast Asia and northern Australia Symptoms: pneumonia, or tissue abscesses and severe sepsis Diagnosis: bacterial culture Treatment: ceftazidime

Diseases in Focus: Common Bacterial Pneumonias A 27-year-old man with a history of asthma is hospitalized with a 4-day history of progressive cough and 2 days of spiking fevers. Gram-positive cocci in pairs are cultured from a blood sample. Can you identify infections that could cause these symptoms?

An optochin-inhibition test of the cultured bacteria, on blood agar. Diseases in Focus: Common Bacterial Pneumonias An optochin-inhibition test of the cultured bacteria, on blood agar.

Viral Pneumonia Viral pneumonia occurs as a complication of influenza, measles, or chickenpox Viral etiology suspected if no other cause is determined

Respiratory Syncytial Virus (RSV) Common in infants; 4500 deaths annually Causes cell fusion (syncytium) in cell culture Symptoms: pneumonia in infants Diagnosis: serological test for viruses and antibodies Treatment: ribavirin, palivizumab

Influenza (Flu) Symptoms: chills, fever, headache, and muscle aches No intestinal symptoms 1% mortality, very young and very old Treatment: zanamivir and oseltamivir inhibit neuraminidase Prophylaxis: multivalent vaccine

2 of 8 RNA segments in genome Figure 24.15 Detailed structure of the influenza virus. 2 of 8 RNA segments in genome NA spike Capsid layer HA spike Envelope © 2013 Pearson Education, Inc.

The Influenza Virus Hemagglutinin (HA) spikes used for attachment to host cells Neuraminidase (NA) spikes used to release virus from cell Antigenic shift Changes in HA and NA spikes Probably due to genetic recombination between different strains infecting the same cell Antigenic drift Point mutations in genes encoding HA or NA spikes May involve only one amino acid Allows virus to avoid mucosal IgA antibodies

Influenza Serotypes Type Antigenic Subtype Year Severity A H3N2 H1N1 1889 1918 1957 1968 1977 Moderate Severe Low B None 1940 C 1947 Very mild

Figure 24.16 Histoplasma capsulatum, a dimorphic fungus that causes histoplasmosis. Yeastlike H. capsulatum Microconidia Macroconidia Yeastlike form typical of growth in tissue at 37°C. Notice that one yeastlike cell to the left of center is budding. The macroconidia are especially useful for diagnostic purposes. Microconidia bud off from hyphae and are the infectious form. At 37°C in tissues, the organism converts to a yeast phase composed of oval, budding yeasts.

Figure 24.17 Histoplasmosis distribution.

Coccidioidomycosis Causative agent: Coccidioides immitis Reservoir: desert soils of American Southwest Symptoms: fever, coughing, weight loss Diagnosis: serological tests Treatment: amphotericin B

Figure 24.18 The life cycle of Coccidioides immitis, the cause of coccidioidomycosis. Human Soil Arthroconidium (about 5 mm long) germinates into tubular hypha. Spherule releases endospores. Tubular hypha Endospores develop within spherule. Hypha begins to segment into arthroconidia. Released endospores spread in tissue—each developing into new spherule Arthroconidia separate from hypha Some arthroconidia return to soil Spherule in tissue (about 30 mm in diameter) Some arthroconidia become airborne Inhaled arthroconidium enlarges and begins to develop into a spherule. Airborne arthroconidium is inhaled.

Figure 24.19 The U.S. endemic area for coccidioidomycosis. 2001 outbreak San Joaquin Valley Areas where disease is known to be endemic

Pneumocystis Pneumonia Causative agent: Pneumocystis jirovecii Reservoir: unknown; possibly humans or soil Symptoms: pneumonia Diagnosis: microscopy Treatment: trimethoprim

Figure 24.20 The life cycle of Pneumocystis jirovecii, the cause of Pneumocystis pneumonia. Mature cyst Cyst Intracystic bodies The mature cyst contains 8 intra-cystic bodies. Each trophozoite develops into a mature cyst. The cyst ruptures, releasing the bodies. Trophozoite The bodies develop into trophozoites. Trophozoite, note extensions for feeding on tissue. The trophozoites divide.

Blastomycosis Causative agent: Blastomyces dermatitidis Reservoir: soil in Mississippi valley area Symptoms: abscesses; extensive tissue damage Diagnosis: isolation of pathogen Treatment: amphotericin B

Other Fungi Involved in Respiratory Disease Systemic Predisposing factors: Immunocompromised state Cancer Diabetes Aspergillus fumigatus Mucor Rhizopus

Diseases in Focus: Diseases of the Lower Respiratory System A worker is hospitalized for acute respiratory illness. He had been near a colony of bats. The mass is surgically removed. Microscopic examination of the mass reveals ovoid yeast cells. Can you identify infections that could cause these symptoms?

Mycelial culture grown from the patient’s lung mass. Diseases in Focus: Microbial Diseases of the Lower Respiratory System Mycelial culture grown from the patient’s lung mass.